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New application of synthetic biology: Justin Vigar, pictured here in a lab in South America, is developing paper-based diagnostics like the paper chip shown on the right, where each dot represents a different test. Image credit: University of Toronto

Justin Vigar and his colleagues are creating a customizable, paper-based platform to rapidly screen for COVID-19 and other infectious diseases using synthetic biology.
“Synthetic biology” might sound like a contradiction in terms, but University of Toronto graduate student Justin Vigar believes it can improve the health and lives of people around the world.

A relatively new field of research, synthetic biology applies engineering principles to recreate fully functional biological systems. In Vigar’s case, he’s using the approach to develop rapid, low-cost diagnostic tools to combat infectious diseases as the recipient of a doctoral award from the Emerging and Pandemic Infections Consortium (EPIC) – one of several U of T institutional strategic initiatives.

Today, the gold standard for diagnosing many infectious diseases is real-time reverse transcription-quantitative PCR (RT-qPCR), which is both sensitive and specific enough to detect small amounts of a particular microbe in a patient sample.

However, the process is complex, requires expensive equipment and materials, and must be carried out by highly trained personnel.

“We talk a lot about South America and other countries in the Global South but in most areas in Canada, including rural Alberta where I grew up, there’s no access to RT-qPCR,” says Vigar, a fourth-year PhD student who is working with Keith Pardee, an associate professor in the Leslie Dan Faculty of Pharmacy.

The lack of access to RT-qPCR testing was especially apparent during the COVID-19 pandemic when many low- and middle-income countries struggled to track the spread of SARS-CoV-2 within their borders because they did not have the infrastructure, expertise and resources to conduct timely RT-qPCR tests for their citizens.

Rapid antigen tests helped fill the void, but they aren’t as sensitive and cannot be scaled up easily to process hundreds of samples at once.

“We wanted to fill that gap by building really accessible tools that could do rapid screening for COVID-19 and other infections – something that would be a midway between a rapid antigen test and RT-qPCR,” says Vigar.

To that end, he and his lab colleagues are using synthetic biology to create a customizable, paper-based platform that uses pocket-sized slips of paper with embedded genetic circuits. The circuitry is built by freeze-drying proteins and other molecular components, which function as amplifiers and sensors, directly onto the paper. Patient samples are minimally processed to extract the genetic material and applied directly to the paper.

If the patient sample contains genetic materials from the pathogen of interest, it will trigger the circuitry to switch on and produce a colour change on the paper, which the naked eye can spot.

Pardee’s team has already proven the effectiveness of their paper-based diagnostic tool in enhancing disease surveillance during Brazil’s 2015-2016 Zika virus outbreak and, more recently, during the COVID-19 pandemic.

Now Vigar is working with collaborators in other Latin American countries and India to expand use of the diagnostic tool to monitor other infectious diseases such as dengue fever and leishmaniasis, which is caused by the Leishmania parasite.

“We have the system working very well in Toronto and a couple of our collaborating countries but the challenge now is sourcing the materials to embed onto the paper and scaling up in other countries,” Vigar says.

While it’s easy for Vigar to get the components and build the paper devices in Toronto and ship them to collaborators around the world, his ultimate goal is to empower them to manufacture and distribute these synthetic biology tools locally.

“We need to work with researchers in other countries to build a network that will give them access to these reagents and materials so they aren’t relying on us to ship it to them. Then they’ll be able to build their own pipelines to detect the pathogens and diseases that they’re interested in.”

Vigar was in Chile for two weeks this past summer to help local researchers to test the reproducibility of their own paper tests. Pardee’s lab also recently hosted two visiting students from Universidad de Los Andes in Columbia to learn the process for building the low-cost devices.

Beyond monitoring infectious diseases in humans, Vigar says the paper-based platforms are being used to answer other important questions – for example, tracking the spread of an agricultural pest or the movements of an endangered species.

Vigar’s passion for synthetic biology and ensuring equitable access to new biotechnologies extends beyond the lab.

He is an active delegate to the United Nations Convention on Biodiversity (UNCBD), which includes two international agreements on biosafety and profit sharing related to synthetic biology and biotechnology.

As an attendee at the UNCBD Conference of the Parties (COP) in Sharm El-Sheikh, Egypt in 2018 and in Montreal in 2022, he educated attendees about synthetic biology and shared his perspective on how low-cost diagnostics can improve the lives of people around the world.

“These technologies are so powerful but they’re limited in where and how they’re used. We want to make it more accessible – and if we work collaboratively toward that goal, it’s going to benefit so many more people.”

Source: University of Toronto